Treatment of Metastatic Colorectal Cancer Patients with 5-Fluorouracil in Combination with Recombinant Subcutaneous Human lnterleukin-2 and Alpha-lnterferon

Abstract

We treated 14 patients with progressive metastatic colorectal cancer, using a combination of subcutaneous recombinant human interleukin-2 (4.8 × 10⁶ IU/m² three times daily on days 1 and 22, and twice daily on days 2 and 23, followed by 2.4 × 10⁶ IU/m² twice daily on days 3-5, 8-12, 24-26, and on 5 consecutive days per week, starting day 29), recombinant human interferon-α2a (5.0 × 10⁶ U/m² thrice weekly), and 5-fluorouracil (750 mg/m² i.v. bolus on days 15-19, and at weekly intervals thereafter, with a 1-week off-therapy interval every 4 weeks). Therapy was continued until disease progression occurred. Four (29%) and 8 (57%) evaluable patients achieved partial remission and stable disease, respectively; median response duration was 5.9 months. Toxicity of this regimen was moderate; the most common side effects were thrombocytopenia, leukopenia, nausea/vomiting, anorexia, malaise and fevers in all patients, along with diarrhea (63%) and mucositis (54%). Less than 10% of patients developed WHO grade IV toxicity; no toxic deaths occurred. Efficacy of this combination was not substantially different from alternative 5-fiuorouracil-based regimens.

Interleukin 2 and interferon alpha-2a do not improve anti-tumour activity of 5-fluorouracil in advanced colorectal cancer

“…Rather than being immunosuppressive, the use of 5-FU + leucovorin appeared to augment natural killer (NK) and lymphokine-activated killer (LAK) activity. Promising clinical results were recently reported by Yang et al (1993) applying a combination of 5-FU, leucovorin and IL-2, and by Atzpodien et al (1994) using a combination of 5-FU, IL-2 and IFNa-2a in metastatic colorectal cancer. These studies provided the basis for the design of the study reported here with a schedule of IL-2, IFNa-2a and 5-FU in patients with advanced colorectal cancer.…”